AIDS (Acquired Immune Deficiency Syndrome), identified for the first time in the early 1980s, is one of the most important diseases in the world. AIDS-treating drugs, developed to date, include protease inhibitors, such as saquinavir, indinavir and ritonavir, and reverse transcriptase inhibitors, such as AZT, ddI, ddC, d4T, 3TC and nevirapine. It is known that when such treating drugs are used alone, they have no significant effect, but when two reverse transcriptase inhibitors, such as AZT and 3TC, and one protease inhibitor, are used in combination, they show a high therapeutic effect.
However, the drug combinations do not improve disease conditions in all patients who were administered them, and moreover they have problems in that they are expensive and have serious side effects, including vomiting and high fever, and appearance of variant viruses having tolerance to these drugs appear.
Accordingly, for better therapy, there is a need to develop a novel class of therapeutic agents, which are more effective and have low toxicity.
AIDS is caused by infection with HIV (human immunodeficiency virus), and at 3-6 weeks after infection, the person suffers from symptoms such as cold and fatigue, for about 1-2 weeks, and then recovered from the symptoms. Thereafter, the long latent period of HIV is lasting for about 10 years. During the long latent period, HIV virus destroys the immune cells of the infected person while it continues to proliferate. Thus, the immune function of the patient is gradually impaired, so that AIDS symptoms appear at the last stage of the latent period.
Among HIV proteins, an nucleocapsid protein (hereinbelow, referred to as ‘NC’) performs not only a structural function of forming virus individuals, but also an important function in the viral life cycle. The major functions of the HIV NC protein are as follows. First, the NC protein is involved in viral genomic encapsidation. This function is attributable to two zinc finger domains consisting of a unique Cys-X2-Cys-X4-His-X4-Cys motif (CCHC motif), and it is known that the domains are highly conserved in all retroviruses and are essential for HIV RNA packaging and infectious virus production. Second, the NC protein is known to promote tRNA primer annealing and strand transfer during viral reverse transcription (RT), and this suggests that the NC protein plays an important role in viral replication. Third, the NC protein has nucleic acid chaperone activity necessary for the viral life cycle, and recently, it was reported that, even when the viral DNA is inserted into the host cell chromosome, the NC protein plays a certain role.
Accordingly, the studies about the NC protein are very important in the view of developing antiviral agent against the essential HIV proteins as well as disclosing biological function of the NC protein during the HIV life cycle.